Trial Outcomes & Findings for Efficacy and Safety Study of Cyclosporine 0.010% to Treat Atopic Keratoconjunctivitis (NCT NCT00884585)

Last Updated: 2012-11-05

Results Overview

Treatment responders are defined as patients with a ≥ 1 grade improvement from baseline in punctate corneal staining score and a ≥ 4 grade improvement from baseline in composite symptom score in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 (0 is ≤2 dots and 5 is \>316 dots (approximately) or ulcer/erosion). The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). The composite symptom score (0 to 15) is the sum of 5 symptoms (each symptom is assessed on a scale of 0=absent to 3=severe).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

176 participants

Primary outcome timeframe

Baseline, Month 2

Results posted on

2012-11-05

Participant Flow

Per protocol defined pre-specified criteria, both eyes could qualify for treatment. However, only one eye was designated as the study eye.

Participant milestones

Participant milestones
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo Followed by COS Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months followed by cyclosporine ophthalmic solution 0.010% up to 9 additional months; at Month 9 the dose may be adjusted to 2 times a day.
Double-Masked Phase (Day 1-Month 3) STARTED	89	87
Double-Masked Phase (Day 1-Month 3) COMPLETED	79	83
Double-Masked Phase (Day 1-Month 3) NOT COMPLETED	10	4
Open-Label Phase (Months 3-9) STARTED	162	0
Open-Label Phase (Months 3-9) COMPLETED	147	0
Open-Label Phase (Months 3-9) NOT COMPLETED	15	0
Open-Label Maintenance (Months 9-12) STARTED	147	0
Open-Label Maintenance (Months 9-12) COMPLETED	144	0
Open-Label Maintenance (Months 9-12) NOT COMPLETED	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety Study of Cyclosporine 0.010% to Treat Atopic Keratoconjunctivitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=89 Participants Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo Followed by COS n=87 Participants Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months followed by cyclosporine ophthalmic solution 0.010% up to 9 additional months; at Month 9 the dose may be adjusted to 2 times a day.	Total n=176 Participants Total of all reporting groups
Age, Customized <18 years	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized 18 to <30 years	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Age, Customized 30 to <50 years	32 Participants n=5 Participants	38 Participants n=7 Participants	70 Participants n=5 Participants
Age, Customized 50 to <65 years	27 Participants n=5 Participants	22 Participants n=7 Participants	49 Participants n=5 Participants
Age, Customized >=65 years	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	39 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	48 Participants n=7 Participants	91 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 2

Population: Intent to Treat: all randomized patients

Outcome measures

Outcome measures
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=89 Participants Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo n=87 Participants Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
Percentage of Treatment Responders	21.3 Percentage of Patients	17.2 Percentage of Patients

SECONDARY outcome

Timeframe: Month 2

Population: Intent to Treat: all randomized patients

Punctate corneal staining responders defined as patients achieving a punctate corneal staining score of 0 or 1 in the study eye. Punctate corneal staining is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is \>2 dots but ≤ 10 dots, 2 is \> 10 dots but ≤ 32 dots, 3 is \> 32 dots but ≤ 100 dots (approximately), 4 is \> 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is \>316 dots (approximately) or ulcer/erosion.

Outcome measures

Outcome measures
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=89 Participants Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo n=87 Participants Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
Percentage of Punctate Corneal Staining Responders	24.7 Percentage of Patients	23.0 Percentage of Patients

SECONDARY outcome

Timeframe: Baseline, Month 2

Population: Intent to Treat: all randomized patients

Composite symptom score improvement is defined as a 4 or more grade decrease from baseline in composite symptom score in the study eye. The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). Each of the 5 symptoms is assessed on a scale of 0=absent to 3=severe. The composite symptom score is the sum of all 5 individual symptom scores, where 0 is no symptoms and 15 is the most severe symptoms.

Outcome measures

Outcome measures
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=89 Participants Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo n=87 Participants Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
Percentage of Patients With an Improvement in the Composite Symptom Score	30.3 Percentage of Patients	28.7 Percentage of Patients

SECONDARY outcome

Timeframe: Baseline, Month 2

Punctate corneal staining improvement is defined as a 1 or more grade decrease from baseline in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is \>2 dots but ≤ 10 dots, 2 is \> 10 dots but ≤ 32 dots, 3 is \> 32 dots but ≤ 100 dots (approximately), 4 is \> 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is \>316 dots (approximately) or ulcer/erosion.

Outcome measures

Outcome measures
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=89 Participants Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo n=87 Participants Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
Percentage of Patients With an Improvement in the Punctate Corneal Staining Score	42.7 Percentage of Patients	42.5 Percentage of Patients

Adverse Events

Cyclosporine Ophthalmic Solution (COS) Followed by COS

Serious events: 11 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=171 participants at risk Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo n=87 participants at risk Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
Injury, poisoning and procedural complications Forearm Fracture	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Infections and infestations Pneumonia	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Immune system disorders Anaphylactic Shock	0.00% 0/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	1.1% 1/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	1.1% 1/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	1.1% 1/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Infections and infestations Infectious Mononucleosis	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Investigations Prostatic Specific Antigen Increased	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis Atopic	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal Hernia	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Vascular disorders Hypertension	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Psychiatric disorders Depression	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Injury, poisoning and procedural complications Joint Injury	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Infections and infestations Herpes Zoster	0.58% 1/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	0.00% 0/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.

Other adverse events

Other adverse events
Measure	Cyclosporine Ophthalmic Solution (COS) Followed by COS n=171 participants at risk Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.	Placebo n=87 participants at risk Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
Eye disorders Allergic Keratitis	14.0% 24/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	11.5% 10/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Eye disorders Blepharitis	5.8% 10/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	3.4% 3/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.
Eye disorders Punctate Keratitis	5.8% 10/171 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.	3.4% 3/87 The Safety Population was used for all adverse event (AE)/serious adverse event (SAE) reporting. All patients in the safety population received at least 1 dose of study medication.

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER